Study to Evaluate PF-04965842 in Patients With Moderate to Severe Psoriasis

A Phase 2, Randomized, Double-blind, Placebo-controlled Study To Evaluate Safety And Efficacy Of Pf-04965842 In Subjects With Moderate To Severe Psoriasis

Study B7451005 is a Phase 2 study which will assess the efficacy and safety of PF-04965842 in patients with moderate to severe psoriasis. The study will include three PF-04965842 groups (200 mg daily, 400 mg daily and 200 mg twice daily) and a placebo group. The treatment period will be 4 weeks in duration and will be followed up by a 4 week follow up period.

Study Overview

• Status: Terminated
• Conditions: Plaque Psoriasis
• Intervention / Treatment: Drug: PF-04965842; Drug: PF-04965842; Drug: PF-04965842; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Surrey, British Columbia, Canada, V3V 0C6
      • Enverus Medical Research
  • Ontario
    • Courtice, Ontario, Canada, L1E 3C3
      • Co-Medica Research Network Inc.
    • Markham, Ontario, Canada, L3P 1X2
      • Lynderm Research Inc.
    • Oakville, Ontario, Canada, L6J 7W5
      • Research by ICLS
    • Peterborough, Ontario, Canada, K9J 5K2
      • Skin Centre For Dermatology
    • Richmond Hill, Ontario, Canada, L4B 1A5
      • The Centre for Dermatology & Cosmetic
    • Waterloo, Ontario, Canada, N2J 1C4
      • K.Papp Clinical Research Inc.
  • Quebec
    • Drummondville, Quebec, Canada, J2B 5L4
      • Dr Isabelle Delorme Inc.
    • Montreal, Quebec, Canada, H2K 4L5
      • Innovaderm Research Inc.
    • Sherbrooke, Quebec, Canada, J1J 2G2
      • Q & T Research Sherbrooke Inc.
• United States
  • Alabama
    • Birmingham, Alabama, United States, 32505
      • Total Skin and Beauty Dermatology Center, PC
  • Arkansas
    • Rogers, Arkansas, United States, 72758
      • Northwest Arkansas Clinical Trials Center, PLLC/Hull Dermatology, PA
  • California
    • Encinitas, California, United States, 92024
      • California Dermatology & Clinical Research Institute
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associates
    • Oceanside, California, United States, 92056
      • Dermatology Specialists, Inc.
    • Pasadena, California, United States, 91105
      • Huntington Medical Foundation/Specialty Office
    • Santa Monica, California, United States, 90404
      • Clinical Science Institute
  • Florida
    • Clearwater, Florida, United States, 33756
      • Olympian Clinical Research
    • Clearwater, Florida, United States, 33756
      • Westcoast Radiology Services
    • Jacksonville, Florida, United States, 32204
      • North Florida Dermatology Associates, PA
    • Miami, Florida, United States, 33144
      • International Dermatology Research, Inc.
    • Orange Park, Florida, United States, 32073
      • Park Avenue Dermatology, PA
    • Ormond Beach, Florida, United States, 32174
      • Leavitt Medical Associates of Florida d/b/a Ameriderm Research
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Advanced Medical Research, Inc
    • Columbus, Georgia, United States, 31904
      • Columbus Regional Research Institute
    • Columbus, Georgia, United States, 31904
      • Columbus Dermatology, P.C.
  • Illinois
    • West Dundee, Illinois, United States, 60118
      • Dundee Dermatology
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Dawes Fretzin Clinical Research Group, LLC
    • Indianapolis, Indiana, United States, 46256
      • Dawes Fretzin Dermatology Group, LLC
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • DS Research
  • Louisiana
    • Lake Charles, Louisiana, United States, 70605
      • Shondra L Smith, MD
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • Clinical Pharmacology Study Group
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center - Section of Dermatology
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center - Shipment Only
    • High Point, North Carolina, United States, 27262
      • Dermatology Consulting Services
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
  • Rhode Island
    • Johnston, Rhode Island, United States, 02919
      • Clinical Partners, LLC
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Health Concepts
  • Texas
    • Arlington, Texas, United States, 76011
      • Arlington Research Center, Inc.
    • Dallas, Texas, United States, 75230
      • Dermatology Treatment & Research Center, PA
    • Houston, Texas, United States, 77004
      • Center For Clinical Studies
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Virginia Clinical Research
  • Washington
    • Spokane, Washington, United States, 99202-1480
      • Premier Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Have a diagnosis of plaque psoriasis for at least 6 months prior to first study dose.
2. Have plaque type psoriasis covering at least 15% of total BSA at Day 1 (at the time of the first study dose).
3. Have a PASI score of 12 or greater at Day 1 (at the time of the first study dose).
4. Be a candidate for phototherapy or systemic treatment of psoriasis (either naïve or history of previous treatment).

Exclusion Criteria:

1. Currently have non plaque forms of psoriasis, eg, erythrodermic, guttate, or pustular psoriasis.
2. 3. Have current drug induced psoriasis, eg, a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium channel blockers, antimalarial drugs or lithium.
3. Have received any of the following treatment regimens specified in the timeframes outlined below:

Within 9 months of first dose of study drug:

• Ustekinumab (Stelara).

Within 12 weeks of first dose of study drug:

• Any experimental therapy for psoriasis or rheumatoid arthritis.

Within 4 8 weeks of first dose of study drug:

• Biologic therapies for psoriasis have discontinuation periods determined from approximately 5x half life of the respective biologic:
• 4 weeks: etanercept (Enbrel).
• 8 weeks: infliximab (Remicade), adalimumab (Humira).

Within 4 weeks of first dose of study drug:

• Systemic treatments other than biologics that could affect psoriasis (eg, oral or injectable corticosteroids, retinoids, methotrexate, cyclosporine, fumaric acid derivatives, sulfasalazine, hydroxycarbamide (hydroxyurea), azathioprine).
• Phototherapy and psoralen plus ultraviolet A therapy (PUVA).
• Other - intramuscular gold, immunization with any live virus vaccination (eg, FluMist), herbal medications.

Within 2 weeks of first dose of study drug:

• Topical treatments that could affect psoriasis (eg, corticosteroids, tars, keratolytics, anthralin, vitamin D analogs, and retinoids).
• Phototherapy with ultraviolet B (UVB) (narrowband or broadband).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 200mg of PF-04965842 twice daily	Drug: PF-04965842; Subjects will receive 200 mg PF 04965842 twice daily for 4 weeks; Other Names: JAK1 inhibitor; Drug: PF-04965842; Subjects will receive 400 mg PF 04965842 daily for 4 weeks; Other Names: JAK1 inhibitor; Drug: PF-04965842; Subjects will receive 200 mg PF 04965842 daily for 4 weeks; Other Names: JAK1 inhibitor
Experimental: Cohort 2; 400mg of PF-04965842 once daily	Drug: PF-04965842; Subjects will receive 200 mg PF 04965842 twice daily for 4 weeks; Other Names: JAK1 inhibitor; Drug: PF-04965842; Subjects will receive 400 mg PF 04965842 daily for 4 weeks; Other Names: JAK1 inhibitor; Drug: PF-04965842; Subjects will receive 200 mg PF 04965842 daily for 4 weeks; Other Names: JAK1 inhibitor
Experimental: Cohort 3; 200mg of PF-04965842 once daily	Drug: PF-04965842; Subjects will receive 200 mg PF 04965842 twice daily for 4 weeks; Other Names: JAK1 inhibitor; Drug: PF-04965842; Subjects will receive 400 mg PF 04965842 daily for 4 weeks; Other Names: JAK1 inhibitor; Drug: PF-04965842; Subjects will receive 200 mg PF 04965842 daily for 4 weeks; Other Names: JAK1 inhibitor
Placebo Comparator: Cohort 4; Placebo comparator daily	Other: Placebo; Subjects will receive placebo for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at Week 4	PASI score is the combined assessment of lesion severity and area affected into single score range: 0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. Body divided into 4 sections (head and neck [h], arms [u], trunk [t], legs [l]); each area scored by itself and scores combined for final PASI score. For each section, percent body surface area (A) of skin involved was estimated: 0 (no involvement) to 6 (90-100 percent involvement), severity estimated by clinical signs: erythema (E), induration (I), scaling (S); 5 point scale: 0 (no involvement) to 4 (very marked involvement). Final PASI score = 0.1Ah (Eh + Ih + Sh) + 0.2Au (Eu + Iu + Su) + 0.3At (Et + It + St) + 0.4Al (El + Il + Sl), where head: 0.1; upper limbs: 0.2; trunk: 0.3; lower limbs: 0.4).	Baseline, Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in PASI Score at Week 1, 2, 3, 4, 5, 6, and 8	PASI score is the combined assessment of lesion severity and area affected into single score range: 0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. Body divided into 4 sections (head and neck [h], arms [u], trunk [t], legs [l]); each area scored by itself and scores combined for final PASI score. For each section, percent body surface area (A) of skin involved was estimated: 0 (no involvement) to 6 (90-100 percent involvement), severity estimated by clinical signs: erythema (E), induration (I), scaling (S); 5 point scale: 0 (no involvement) to 4 (very marked involvement). Final PASI score = 0.1Ah (Eh + Ih + Sh) + 0.2Au (Eu + Iu + Su) + 0.3At (Et + It + St) + 0.4Al (El + Il + Sl), where head: 0.1; upper limbs: 0.2; trunk: 0.3; lower limbs: 0.4).	Baseline, Week 1, 2, 3, 4, 5, 6, 8
Change From Baseline in PASI Score at Week 1, 2, 3, 5, 6 and 8	PASI score is the combined assessment of lesion severity and area affected into single score range: 0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. Body divided into 4 sections (head and neck [h], arms [u], trunk [t], legs [l]); each area scored by itself and scores combined for final PASI score. For each section, percent body surface area (A) of skin involved was estimated: 0 (no involvement) to 6 (90-100 percent involvement), severity estimated by clinical signs: erythema (E), induration (I), scaling (S); 5 point scale: 0 (no involvement) to 4 (very marked involvement). Final PASI score = 0.1Ah (Eh + Ih + Sh) + 0.2Au (Eu + Iu + Su) + 0.3At (Et + It + St) + 0.4Al (El + Il + Sl), where head: 0.1; upper limbs: 0.2; trunk: 0.3; lower limbs: 0.4).	Baseline, Week 1, 2, 3, 5, 6, 8
Percentage of Participants Achieving 50 Percent Reduction From Baseline PASI Score at Week 1, 2, 3, 4, 5, 6, and 8	PASI score is combined assessment of lesion severity and area affected into single score range:0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. Body divided into 4 sections (head and neck [h], arms [u], trunk [t], legs [l]); each area scored by itself and scores combined for final PASI score. For each section, percent body surface area (A) of skin involved was estimated:0 (no involvement) to 6 (90-100 percent involvement), severity estimated by clinical signs: erythema (E), induration (I), scaling (S); 5 point scale: 0 (no involvement) to 4 (very marked involvement). Final PASI score = 0.1Ah (Eh + Ih + Sh) + 0.2Au (Eu + Iu + Su) + 0.3At (Et + It + St) + 0.4Al (El + Il + Sl), where head: 0.1; upper limbs: 0.2; trunk: 0.3; lower limbs: 0.4). Participants who had at least 50 percent reduction in PASI score relative to baseline PASI Score are reported. 90 percent confidence intervals are calculated using clopper-pearson (exact) method.	Baseline, Week 1, 2, 3, 4, 5, 6, 8
Percentage of Participants Achieving 75 Percent Reduction From Baseline PASI Score at Week 1, 2, 3, 4, 5, 6 and 8	PASI score is combined assessment of lesion severity and area affected into single score range:0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. Body divided into 4 sections (head and neck [h], arms [u], trunk [t], legs [l]); each area scored by itself and scores combined for final PASI score. For each section, percent body surface area (A) of skin involved was estimated:0 (no involvement) to 6 (90-100 percent involvement), severity estimated by clinical signs: erythema (E), induration (I), scaling (S); 5 point scale: 0 (no involvement) to 4 (very marked involvement). Final PASI score = 0.1Ah (Eh + Ih + Sh) + 0.2Au (Eu + Iu + Su) + 0.3At (Et + It + St) + 0.4Al (El + Il + Sl), where head: 0.1; upper limbs: 0.2; trunk: 0.3; lower limbs: 0.4). Participants who had at least 75 percent reduction in PASI score relative to baseline PASI Score are reported. 90 percent confidence intervals are calculated using clopper-pearson (exact) method.	Baseline, Week 1, 2, 3, 4, 5, 6, 8
Percentage of Participants Achieving 90 Percent Reduction From Baseline PASI Score at Week 1, 2, 3, 4, 5, 6, and 8	PASI score is combined assessment of lesion severity and area affected into single score range:0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. Body divided into 4 sections (head and neck [h], arms [u], trunk [t], legs [l]); each area scored by itself and scores combined for final PASI score. For each section, percent body surface area (A) of skin involved was estimated:0 (no involvement) to 6 (90-100 percent involvement), severity estimated by clinical signs: erythema (E), induration (I), scaling (S); 5 point scale: 0 (no involvement) to 4 (very marked involvement). Final PASI score = 0.1Ah (Eh + Ih + Sh) + 0.2Au (Eu + Iu + Su) + 0.3At (Et + It + St) + 0.4Al (El + Il + Sl), where head: 0.1; upper limbs: 0.2; trunk: 0.3; lower limbs: 0.4). Participants who had at least 90 percent reduction in PASI score relative to baseline PASI Score are reported. 90 percent confidence intervals are calculated using clopper-pearson (exact) method.	Baseline, Week 1, 2, 3, 4, 5, 6, 8 (early termination)
Percentage of Participants Achieving Physician Global Assessment (PGA) Response of 'Clear' or 'Almost Clear' at Week 1, 2, 3, 4, 5, 6, and 8	The PGA of psoriasis was scored on a 5-point scale, reflecting a global consideration of the erythema (E), induration (I), and scaling (S) across all psoriatic lesions. The severity rating scores (erythema: 0= no evidence of erythema to 4= dark, deep red; Induration: 0= no evidence of plaque elevation to 4= marked plaque elevation, hard/sharp borders; Scaling: 0= no evidence of scaling to 4= thick, coarse scale predominates) were summed (E + I + S= total) and the average (total/3) was taken. The total average was rounded to the nearest whole number score to determine the PGA. The 5-point scale for PGA was: 0= clear; 1= almost clear; 2= mild; 3= moderate; 4= severe, where higher score indicating more severity. Participants with response of clear and almost clear were reported. 90 percent confidence intervals were calculated using clopper-pearson (exact) method.	Week 1, 2, 3, 4, 5, 6, 8
Change From Baseline in Fasting Lipids at Week 2, 4 and 8	Participants were required to fast 9 hours prior to sampling for lipid profile which included following parameters: low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), cholesterol, triglycerides.	Baseline, Week 2, 4, 8 (early termination)
Change From Baseline in Lipid Ratios at Week 2, 4 and 8	The ratio of LDL-C/HDL-C was reported.	Baseline, Week 2, 4, 8 (early termination)
Change From Baseline in High Sensitivity C- Reactive Protein (hsCRP) at Week 1, 2, 3, 4, and 8	The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. Reference range for measurements is 0-0.5 mg/dL and lower limit of detection is less than (<) 0.015 mg/dL. Any value <0.015 mg/dL is imputed as 0.0075 mg/dL.	Baseline, Week 1, 2, 3, 4, 8 (early termination)
Number of Participants Reporting Clinically Significant Change From Baseline in Epstein-Barr Virus (EBV) Values	EBV samples were collected and changes from baseline were evaluated by the principal investigator (PI) for clinical significance. Clinical significance is levels outside of the normal range (abnormal levels) with clinically apparent viral disease, or that resulted in adverse event (AEs) or required follow-up.	Baseline up to Week 8 (early termination)
Number of Participants Reporting Clinically Significant Change From Baseline in Cytomegalovirus (CMV) Values	CMV samples were collected and changes from baseline were evaluated by the PI for clinical significance. Clinical significance is levels outside of the normal range (abnormal levels) with clinically apparent viral disease, or that resulted in AEs or required follow-up.	Baseline up to Week 8 (early termination)
Number of Participants Reporting Clinically Significant Change From Baseline in Herpes Simplex Virus Deoxyribonucleic Acid (HSV DNA) Values	HSV DNA samples were collected and changes from baseline were evaluated by the PI for clinical significance. Clinical significance is levels outside of the normal range (abnormal levels) with clinically apparent viral disease, or that resulted in AEs or required follow-up.	Baseline up to Week 8 (early termination)
Change From Baseline in Blood Pressure (BP) at Week 1, 2, 3, 4, 5, 6, and 8		Baseline, Week 1, 2, 3, 4, 5, 6, 8 (early termination)
Change From Baseline in Pulse Rate at Week 1, 2, 3, 4, 5, 6, and 8		Baseline, Week 1, 2, 3, 4, 5, 6, 8 (early termination)
Change From Baseline in Respiratory Rate at Week 1, 2, 3, 4, 5, 6, and 8		Baseline, Week 1, 2, 3, 4, 5, 6, 8 (early termination)
Change From Baseline in Body Temperature at Week 1, 2, 3, 4, 5, 6, and 8		Baseline, Week 1, 2, 3, 4, 5, 6, 8 (early termination)
Number of Participants Reporting Clinically Significant Change From Baseline in Heart Rate		Baseline up to Week 8 (early termination)
Number of Participants Reporting Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters	ECG change data was reported as qualitative results, as per change in planned analysis. It was categorized as: normal; abnormal, not clinically significant or abnormal, clinically significant.	Baseline up to Week 8 (early termination)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Wojciechowski J, Malhotra BK, Wang X, Fostvedt L, Valdez H, Nicholas T. Population pharmacokinetic-pharmacodynamic modelling of platelet time-courses following administration of abrocitinib. Br J Clin Pharmacol. 2022 Aug;88(8):3856-3871. doi: 10.1111/bcp.15334. Epub 2022 Apr 11.
• Wojciechowski J, Malhotra BK, Wang X, Fostvedt L, Valdez H, Nicholas T. Population Pharmacokinetics of Abrocitinib in Healthy Individuals and Patients with Psoriasis or Atopic Dermatitis. Clin Pharmacokinet. 2022 May;61(5):709-723. doi: 10.1007/s40262-021-01104-z. Epub 2022 Jan 21. Erratum In: Clin Pharmacokinet. 2022 Apr;61(4):591.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: July 24, 2014
• First Submitted That Met QC Criteria: July 24, 2014
• First Posted (Estimate): July 28, 2014

Study Record Updates

• Last Update Posted (Estimate): October 5, 2016
• Last Update Submitted That Met QC Criteria: August 11, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: safety; placebo; efficacy; JAK; janus kinase; psoriasis; severe; moderate; plaque; randomized; double-blind; Phase 2
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Abrocitinib
• Other Study ID Numbers: B7451005; JAK-1 FOR PSORIASIS (Other Identifier: Alias Study Number)